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PXD035420-2

PXD035420 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSubstrate spectrum of PPM1D in the cellular response to DNA double strand breaks
DescriptionPPM1D (also known as WIP1) is a p53-regulated protein phosphatase that modulates the DNA damage response (DDR) by dephosphorylation of DDR proteins. Amplification of PPM1D gene or gain-of-function mutations are commonly found in cancer. Here, we employed chemical inhibition of PPM1D and quantitative mass spectrometry-based phosphoproteomics to identify the substrates of PPM1D upon induction of DNA double strand breaks (DSBs) by topoisomerase II poison etoposide. We identified 73 putative PPM1D substrates that are involved in DNA repair, regulation of transcription and RNA processing. One third of DSB-induced S/TQ phosphorylation sites are dephosphorylated by PPM1D, demonstrating that PPM1D only partially counteracts ATM/ATR/DNA-PK signaling. PPM1D-targeted phosphorylation sites are found in a specific amino acid sequence motif that is characterized by glutamic acid residues, high intrinsic disorder and poor evolutionary conservation. We identified a functionally uncharacterized protein Kanadaptin as ATM and PPM1D substrate upon DSB induction. We propose that PPM1D plays a role during the response to DSBs formation by regulating the phosphorylation of DNA- and RNA-binding proteins in intrinsically disordered regions.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:57:30.011.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPetra Beli
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-20 01:07:33ID requested
12022-09-06 04:15:10announced
22023-11-14 08:57:30announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Double strand breaks, ATM, WIP1, Kanadaptin,PPM1D, DNA damage
Contact List
Petra Beli
contact affiliationInstitute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany
contact emailp.beli@imb-mainz.de
lab head
Petra Beli
contact affiliationInstitute of Molecular Biology (IMB), Mainz, Germany
contact emailp.beli@imb-mainz.de
dataset submitter
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Dataset FTP location
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